The Human Gene Mapping Program maintains an ongoing collaborative interaction with both intramural and extramural laboratories. This project carries out physical and genetic mapping using three principle technologies. Southern blotting analysis of rapidly proliferating human X rodent somatic cell hybrid DNA is used for the assignment of gene sequences to specific chromosomes. Secondly, fluorescence in situ chromosome hybridization, which has replaced isotopic hybridization, provides precise regional localization of target sequences with a minimum of background. Finally, segregation or linkage analysis of polymorphic genes or DNA markers is carried out using the Centre D'Etude du Polymorphisme Humain (CEPH) reference families which contain about 50 three-generation pedigrees. These methodologies have resulted in the assignment of a number of cytokines, G-protein coupled receptors, cellular oncogenes, novel tyrosine kinases, and regulatory DNA binding proteins. In addition, a study is underway to construct a high resolution linkage and cytogenetic map of chromosome 3. Ultimately, these maps will lead to the isolation and characterization of tumor suppressor genes involved in both familial and non-familial cancer and in determining the breakpoints of chromosomal rearrangements in certain diseases. The principal investigator serves in the human genome initiative as well as chairman of the International Committee on Comparative Gene Mapping.